title: Study of membrane-induced conformations of substance P: detection of extended polyproline II helix conformation.
abstract: We study the conformation of substance P (SP), a ligand of neurokinin 1 receptor, and its analogue [Trp8]SP in membrane-mimetic media to provide further insights into membrane-ligand interactions and the factors determining and modulating the peptide structure. CD data revealed that the neuropeptide attains α-helical fold in negatively charged SDS micelles and DMPG liposomes but not in zwitterionic DMPC. The fluorescence experiments reported that the Trp side chain of [Trp8]SP inserts into the hydrophobic core of the SDS micelles and DMPG liposomes but faces the DMPC hydrophilic region, indicating that electrostatic interactions between membrane and SP are essential for the α-helical fold. Formation of extended polyproline II (PPII) helical structure in aqueous solutions and in submicellar concentrations of SDS and DMPC liposomes was confirmed by comparing CD spectra at increasing temperatures. Moreover, in all conditions where PPII conformation was detected, the Trp was totally exposed to the bulk. The PPII structure may be vital for recognition processes of SP by neurokinin receptors.
authors.affiliation: Unitat de Biofísica, Departament de Bioquímica i de Biologia Molecular, and Centre d'Estudis en Biofísica, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Arash
authors.initials: A
authors.lastname: Foroutan
authors.forename: Tzvetana
authors.initials: T
authors.lastname: Lazarova
authors.forename: Esteve
authors.initials: E
authors.lastname: Padrós
mesh_terms: D002942:Circular Dichroism; D008081:Liposomes / Q000737:chemistry*; D008823:Micelles; D010455:Peptides / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry; D017433:Protein Structure, Secondary; D018040:Receptors, Neurokinin-1 / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013373:Substance P / Q000737:chemistry*; D013696:Temperature
chemical_list: D008081:Liposomes; D008823:Micelles; D010455:Peptides; D010715:Phosphatidylglycerols; D018040:Receptors, Neurokinin-1; C011083:polyproline; D013373:Substance P; D012967:Sodium Dodecyl Sulfate; C002773:dimyristoylphosphatidylglycerol